Monday, January 21, 2013

The Coming Influenza Pandemic (Part I)

As 2012-2013
shapes up to be a particularly bad year for seasonal flu, it is worth
remembering that even during a good year, influenza kills an average of more
than 30,000 Americans. More disturbingly, every 30-50 years the world sees a
particularly deadly pandemic strain that kills hundreds of thousands or even millions
of people.

When talking
about plagues, pandemics and infectious holocausts, people generally think of
modern day plagues, such as AIDS, which had killed 25 million people by 2008,2or ancient ones, like the Black Death, which
killed an estimated 75-100 million people over the 50 years between 1348 and
1400.9Many people don’t realize that the deadliest
pandemic of all time was the Influenza pandemic of 1918-1919, which killed
between 50 and 100 million people in just 2 years.3(p25)25 million people may have died in just the
first 25 weeks of the pandemic.10Over 15 million people died in India. 14% of
Fiji and 20% of Western Samoa perished. In Europe, 250,000 British and 400,000
French died. In the U.S., five to six hundred thousand people died. Entire
villages in Alaska were wiped out.10 Overall, morbidity rates were
close to 50% and mortality rates ranged from 10 to 20%.7,10

Because
seasonal influenza returns each year and most adults have fairly robust immune
responses due to repeated exposures to related influenza strains over their lifetimes,
people tend to think of influenza as an unpleasant, but relatively harmless
pest. The reality is that even the seasonal flu kills thirty to forty thousand
Americans per year,3(p22) while killing hundreds of thousands worldwide.7 Most of those who die are elderly, very young,
immune-compromised, poor or malnourished.3(p22)However,
a deadly strain, such as the 1918 influenza strain, can harm anyone due to its
particular virulence and novelty, which leaves much of society lacking in any
immunity.7

The name
Spanish Flu is a misnomer, as the outbreak did not start in Spain, nor was
Spain the hardest hit. The pandemic came in the midst of World War I. Most
European countries, as well as the U.S., were censoring their media. Spain,
being a neutral country, was one of the first to accurately report on this
deadly new disease.10

Some
scientists speculate that the pandemic started in a U.S. military barracks in
Boston or Kansas in early 1918, from a mutated influenza virus that originated
in China.10From there it spread to Brest, France, with
U.S. soldiers as the primary vectors. In the early stages of the outbreak, it
resembled a typical flu season, with the elderly and sick being the hardest
hit. By August, a second, deadlier wave of the virus hit Europe, the U.S. and
Sierra Leone. Because the world was entrenched in a bloody war, many of those
who were infected either stayed in the trenches, spreading the disease to their
comrades and enemies, or were placed on transport trains and sent to field
hospitals, where they spread the more virulent form of the disease to
civilians.10

Influenza
generally hits the very young and old the hardest, but it usually kills less
than 1% of those who are infected.7The 1918 pandemic was unusual in that it
killed 10-20% of those infected, many of whom were young adults and otherwise
healthy people. The elderly seemed to have had some degree of immunity. There
had been another pandemic in 1889, known as the Russian flu. Many scientists
believe that older people may have had some immunity to the 1918 strain through
their exposure to this 1889 strain.10 Everyone else had little or no immunity;
hence, the high morbidity rates.3,10

So where did
this new strain come from? What made it so virulent? Why did pandemic influenza
disappear for 29 years and then return in such a deadly and highly
transmissible form? Could it happen again?

Influenza,
is an RNA virus in the Orthomyxoviridae family.13The enzymes that replicate RNA, unlike those
that copy DNA, tend not to have the ability to proofread and repair mistakes.
As a result, RNA viruses mutate rapidly, producing new forms that can evade our
immune systems, leaving us vulnerable to infection. 3(p15),7Occasionally, these new forms are also
particularly virulent, increasing the likelihood of death once we are infected.
To make matters worse, influenza can readily swap genes with other influenza
viruses. Thus, if a suitable vector, such as a pig, is infected with two
different strains, a new strain can develop that is either particularly
infectious or particularly virulent, or both, like the 1918 strain.

Influenza A
is endemic and usually harmless in birds, but it can cause serious illness in
humans.3,7
It is responsible for the majority of seasonal flu cases.13(p582)Influenza A mutates rapidly and is readily
able to swap genes with other influenza strains.3,7Some strains have the ability to infect
multiple species. This is particularly dangerous and gives it high potential
for creating deadly pandemics.3,7

Influenza B
is endemic in humans, but rare in other species.7It is usually very mild.13It mutates 2-3 times more slowly than
Influenza A.7The combination of low mutation rate and low
zoonotic potential makes Influenza B a very unlikely candidate for a deadly
pandemic and, therefore, has very low pandemic potential.7

Influenza C
can infect humans and some other mammals.7It is usually mild and generally infects only
children, though occasionally it does cause severe illness and epidemics. It is
also considered to have low pandemic potential.7,13

Hemagglutinin
(HA) is a glycoprotein in the surface of the influenza virus that causes red
blood cells to agglutinate.3,7,13It is the molecular key that allows theinfluenza virus to enter the host cell. It is
also considered an antigen, since it can stimulate the production of antibodies
against it. Avian hemagglutinins can usually only infect avian gut cells;
whereas human hemagglutinins can usually only unlock human respiratory cells.
The species barrier between birds and humans is high (i.e., it is difficult for
pure avian flu to mutate directly to a human flu). However, transmission
between pigs and birds is relatively easy and the barrier between swine and
humans is low. Hence, swine are an ideal mixing pot for mammalian and avian
antigens.3,
p17

Neuraminidase
is an enzyme that aids in cell lysis and the escape of virions from host cells.
It is another antigen on the surface of the influenza virus.3,7,13Oseltamivir (trade name Tamiflu) is a
neuraminidase inhibitor that functions by blocking the escape of new influenza
virions from host cells, thus halting the progression and spread of the
disease. It is one of the only drugs able to stop H5N1 and H1N1 influenza. 3(p19),7

Influenza
strains are named for the types of surface antigens in their envelopes. H1N1
has hemagglutinin 1 and neuraminidase 1, whereas H5N1 has hemagglutinin 5 and
neuraminidase 1. There are 16 known HA antigens and 9 known NA antigens.7